Various apheresis procedures require the use of anticoagulants such as acid citrate dextrose ("ACD") or heparin to prevent hemostasis and to permit blood processing. The rate of blood flow and, therefore, the time required to complete a procedure are related to the allowable anticoagulant level in the donor (in the case of a person donating a blood component) or in the patient (in the case of a person whose blood is being treated). If the anticoagulant level in the tubing set is too low, the blood will clot. If the anticoagulant level in the donor/patient is too high, adverse physiological reactions may occur. For example, ACD interferes with clotting by binding with ionized calcium, and excessive ACD levels can result in chills or convulsions. Heparin may cause flushing or hypotension, and its anticoagulant effects (it has a half life of about four hours) can last dangerously long after the procedure is completed. It is therefore desirable to carefully control the anticoagulant level.
In the past, anticoagulant levels have been controlled indirectly and imprecisely by controlling the rate of infusion of anticoagulant into the tubing set, without any direct control on the rate of infusion of anticoagulant into the donor/patient. That approach is not exact because it does not account for the anticoagulant that is removed from the tubing set by the procedure itself. The removed anticoagulant never enters the donor/patient. For example, a significant volume of anticoagulant is drawn off in the plasma collect line in plasma collection procedures and in the cell collect line in cell collection procedures. In addition, that approach does not account for anticoagulant added to the tubing set by the donor/patient due to the recirculation of unmetabolized anticoagulant from the donor/patient into the inlet line, nor does it account for anticoagulant added to the tubing set by the replacement fluid.
There are many prior art systems for controlling various flow rates in a tubing set, but it is believed that these systems are not applicable to the control of anticoagulant flow rates and concentrations in the manner of the present invention. For example, U.S. Pat. No. 4,582,598 by Bilstad discloses a system in which the collection rate and the replacement fluid rate are continuously monitored and adjusted by a control means that is responsive to measurement signals; U.S. Pat. Nos. 4,447,191 and 4,501,531 by Bilstad include a control circuit for adjusting the anticoagulant pump rate and for discontinuing the anticoagulant pumping in case a failsafe system detects an air bubble or other tripping event. It appears that none of these patents disclose a method for adjusting anticoagulant infusion rates to maintain a desired anticoagulant flow rate or concentration by considering the additive and subtractive effects of the tubing circuit or the recirculation of unmetabolized anticoagulant from the donor/patient.
U.S. Pat. No. 4,769,001 by Prince describes a system for calibrating an anticoagulant pump and a blood pump by monitoring the pressure in the line between the two pumps. Neither of these patents teaches a method for maintaining a desired anticoagulant flow rate or concentration by adjusting the anticoagulant infusion rate to account for variations caused by collection, replacement and recirculation.
U.S. Pat. No. 4,968,295 by Neumann discloses a blood separation apparatus in which centrifuge speeds are automatically varied in response to blood flow rates so that the volume ratios of the fractions remain constant. The apparatus includes an anticoagulant control wherein the anticoagulant infusion rate is varied as a linear function of the blood flow rate, but without considering collection, replacement or recirculation effects.
Other systems in which anticoagulant infusion rates may be directly or indirectly controlled include those described in U.S. Pat. Nos. 4,817,045 by Faeser; 4,923,598 by Schal; 4,655,742 by Vantard; 4,648,866 by Malbrancq; 4,573,961 by King; 4,795,314 by Prybella; 4,657,529 by Prince; and 4,995,268 by Ash. As in the other art described more particularly above, none of these teaches a method for varying the anticoagulant infusion rate to account for collection, replacement and withdrawal effects.
Anticoagulant levels can be expressed in several ways, including concentration, volume and flow rate. For purposes of this patent, "concentration" of anticoagulant refers to the volume fraction of anticoagulant in a fluid. "Flow rate" refers to the volume of flowing fluid per unit of time. As explained below, the important anticoagulant levels are typically the concentration of anticoagulant in the donor/patient and the flow rate and concentration of anticoagulant in the inlet line and the return line to the donor/patient. It will be apparent to those skilled in the art that these levels are related to one another and can be expressed in other terms (for example, the flow rate of anticoagulant in the return line can be expressed as the flow rate of fluid in the return line times the anticoagulant concentration in the return line). Unless otherwise specified, the term "level" in the claims will refer to any of, and any combination of, flow rate, concentration and volume. It will also be apparent to those skilled in the art that although it is convenient to express fluid quantities in terms of volume, the invention also includes quantities expressed in terms of weight by making appropriate adjustments to account for the specific gravities of the fluids.